Exclusively breastmilk‐fed preterm infants are at high risk of developing subclinical vitamin K deficiency despite intramuscular prophylaxis at birth

BACKGROUND: There is near‐global consensus that all newborns be given parenteral vitamin K(1) (VK(1)) at birth as prophylaxis against VK deficiency bleeding (VKDB). Breastmilk has a low VK content and cases of late VKDB are reported in exclusively breastmilk‐fed preterm infants despite VK prophylaxis at birth. OBJECTIVES: To assess the prevalence of functional VK insufficiency in preterm infants based on elevated under‐γ‐carboxylated (Glu) species of Gla proteins, factor II (PIVKA‐II), and osteocalcin (GluOC), synthesized by liver and bone, respectively. PATIENTS/METHODS: Prospective, multicenter, observational study in preterm infants born <33 weeks' gestation. Blood samples and dietary history were collected before hospital discharge, and after discharge at 2–3 months’ corrected age. Outcome measures were serum VK(1), PIVKA‐II, and %GluOC (GluOC as a percentage of the sum of GluOC plus GlaOC) compared between exclusively breastmilk‐fed and formula/mixed‐fed infants after discharge. RESULTS: After discharge, breastmilk‐fed babies had significantly lower serum VK(1) (0.15 vs. 1.81 μg/L), higher PIVKA‐II (0.10 vs. 0.02 AU/ml) and higher %GluOC (63.6% vs. 8.1%) than those receiving a formula/mixed‐feed diet. Pre‐discharge (based on elevated PIVKA‐II), only one (2%) of 45 breastmilk‐fed infants was VK insufficient. After discharge, eight (67%) of 12 exclusively breastmilk‐fed babies were VK insufficient versus only one (4%) of 25 formula/mixed‐fed babies. CONCLUSIONS: Preterm infants who remain exclusively or predominantly human breastmilk‐fed after neonatal unit discharge are at high risk of developing subclinical VK deficiency in early infancy. Routine postdischarge VK(1) supplementation of breastfed infants to provide intakes comparable to those from formula milks should prevent this deficiency.